Marelyn Wintour

Can Excess Glucocorticoid, in Utero, Predispose to Cardiovascular and Metabolic Disease in Middle Age?

For many years, both human and animal studies correlated changes in behaviour of the young offspring with the degree of maternal stress or glucocorticoid exposure of the foetus/neonate. In the past ten years there has been overwhelming epidemiological evidence to suggest that growth retardation in utero is a very important risk factor for the development of cardiovascular and metabolic disease in adult life. More recently, it has been shown that one important, even key, determinant is the exposure of the foetus to excess glucocorticoid. Even a brief period (48 h) of dexamethasone exposure very early in pregnancy was able to programme permanently hypertensive adult sheep. Understanding how such programming works, and the underlying physiological changes that occur, provides one of the most exciting challenges in contemporary endocrinology and developmental biology.

Effect of Variations of Plasma Sodium Concentration on the Adrenal Response to Angiotensin II

The secretion rate of aldosterone was increased by infusion of valine-5-angiotensin II into the adrenal arterial blood supply of sheep. The dimensions of the increase in aldosterone output were inversely related to the control plasma concentration. This high aldosterone secretion was reduced substantially by concurrent adrenal infusion of concentrated NaCl solution which increased plasma sodium concentration by approximately 10 meq/liter. The reduction of aldosterone secretion occurred within 20 minutes. Angiotensin II infusion did not increase the secretion rates of cortisol or corticosterone. The significance of the finding that environmental sodium concentration has different effects on the aldosterone-stimulating action and the pressor action of angiotensin II is discussed.